Summary: (1) The activation of latent retroviruses was studied in cultures of human and non-human primate cells. Cells were treated with agents known to induce viral replication and were subsequently examined by TEM for the presence of retroviral particles. All of the inducing agents and protocols failed to cause replication of latent retroviruses in primate cells although they caused specific induction of Type A and Type C retrovirus particles in murine cells (with A. Khan, CBER, DVP) (2) Differences in replication and cellular pathologic effects between the lab strains of Simian Foamy Viruses (SFV) and SFVs isolated from naturally occurring infections in macaques are being investigated by TEM. (with A. Khan, CBER, DVP) (3) The EM lab participates in a research project related to vaccine development with Dr. I Berkower (CBER, DVP). The goal of these studies is to enhance the immunologic response to HIV by creating novel multimeric hybrid particles containing the HIV gp120 envelope molecule. After isolation and purification, the assembly of the hybrids into stable multimeric particles is assessed by TEM. (4) The association of influenza virus matrix protein (M) with ribonucleoproteins (RNP) may control viral growth and morphology. Results show that virus strains with stronger binding of M to RNP have higher replication efficiency and spherical morphology; whereas those with weaker M to RNP binding replicate less efficiently and have a filamentous morphology. (with Z. Ye, CBER, DVP) (5) Herpes simplex virus injected directly into mouse brain was found to replicate in the ciliated ependymal cells lining the ventricles. Viral replication caused swelling, disruption, and sloughing of the infected ependymal cells. (with N. Markovitz, CBER, DCGT) (6) Melanin synthesis takes place in membrane-bound cytoplasmic structures termed melanosomes. The biogenesis and maturation of melanosomes is accompanied by a morphological transition from an amorphous, rounded vesicle into an elongated, fibrillar structure. However, the sequence in which melanosomal proteins are sorted to the organelle and the role(s) they play in its maturation remain largely unknown. In this study melanosome fractions were prepared by sucrose density gradient centrifugation followed by free-flow electrophoresis. They were characterized by TEM for purity and predominant melanosome stage and by tandem mass spectrometry and Western immunoblotting for specific proteins. (with V. Hearing, NCI)